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 Blood, 12 March 2009, Vol. 113, No. 11, pp. 2595-2604.
Prepublished online as a Blood First Edition Paper on December 12, 2008; DOI 10.1182/blood-2008-10-182246.

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TRANSPLANTATION

Mesenchymal stem cell–mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice

Takayoshi Yamaza1,*, Yasuo Miura2,*, Kentaro Akiyama1, Yanming Bi3, Wataru Sonoyama1, Stan Gronthos4, WanJun Chen3, Anh Le1, and Songtao Shi1

1 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles; 2 Graduate School of Medicine, Kyoto University, Kyoto, Japan; 3 National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD; and 4 Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia

Subcutaneous transplants of bone marrow mesenchymal stem cells (BMMSCs) are capable of generating ectopic bone and organizing functional hematopoietic marrow elements in animal models. Here we report that immunocompromised mice received subcutaneous BMMSC transplants using hydroxyapatite tricalcium phosphate as a carrier suppressed age-related degeneration in multiple organs and benefited an increase in life span extension compared with control littermates. The newly organized ectopic bone/marrow system restores active hematopoiesis via the erythropoietin receptor/signal transducer and activator of transcription 5 (Stat5) pathway. Furthermore, the BMMSC recipient mice showed elevated level of Klotho and suppression of insulin-like growth factor I signaling, which may be the mechanism contributing to the alleviation of aging-like phenotypes and prolongation of life in the treated mice. This work reveals that erythropoietin receptor/Stat5 pathway contributes to BMMSC-organized ectopic hematopoiesis, which may offer a treatment paradigm of reversing age-related degeneration of multiple organs in adult immunocompromised mice.


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